El-Say Khalid M, Abd-Allah Fathy I, Lila Ahmed E, Hassan Abd El-Saboor A, Kassem Alaa Eldin A
a Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , King Abdulaziz University , Jeddah , Saudi Arabia and.
b Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , Al-Azhar University , Cairo , Egypt.
J Liposome Res. 2016;26(1):57-68. doi: 10.3109/08982104.2015.1029495. Epub 2015 Apr 8.
The purpose of this study was to load diacerein (DCR) in niosomes by applying response surface methodology and incorporate these niosomes in gel base for topical delivery. Box-Behnken design was used to investigate the effect of charge-inducing agent (X1), surfactant HLB (X2) and sonication time (X3) on the vesicle size (Y1), entrapment efficiency (Y2) and cumulative drug released (Y3). DCR niosomal formulations were prepared by thin film hydration method. The optimized formula was incorporated in different gel bases. DCR niosomal gels were evaluated for homogeneity, rheological behavior; in vitro release and pharmacodynamic activity by carrageenan-induced hind paw edema method in the rat compared with DCR commercial gel. The results revealed that the mean vesicle sizes of the prepared niosomes ranged from 7.33 to 23.72 µm and the entrapment efficiency ranged from 9.52% to 58.43% with controlled release pattern over 8 h. DCR niosomal gels exhibited pseudoplastic flow with thixotropic behavior. The pharmacodynamic activity of DCR niosomal gel in 3% HPMC showed significant, 37.66%, maximum inhibition of edema size in comparison with 20.83% for the commercial gel (p < 0.05). These results recommended the incorporation of DCR niosomes in 3% HPMC for topical application as a potent anti-inflammatory drug for the treatment of osteoarthritis.
本研究的目的是通过应用响应面法将双醋瑞因（DCR）载入非离子表面活性剂囊泡中，并将这些非离子表面活性剂囊泡掺入凝胶基质中用于局部给药。采用Box-Behnken设计研究电荷诱导剂（X1）、表面活性剂亲水亲油平衡值（HLB）（X2）和超声处理时间（X3）对囊泡大小（Y1）、包封率（Y2）和药物累积释放量（Y3）的影响。通过薄膜水化法制备DCR非离子表面活性剂囊泡制剂。将优化后的配方掺入不同的凝胶基质中。与DCR市售凝胶相比，通过角叉菜胶诱导大鼠后爪水肿法对DCR非离子表面活性剂囊泡凝胶进行均匀性、流变学行为、体外释放和药效学活性评价。结果显示，所制备的非离子表面活性剂囊泡的平均囊泡大小在7.33至23.72 µm之间，包封率在9.52%至58.43%之间，且在8小时内具有控释模式。DCR非离子表面活性剂囊泡凝胶表现出具有触变性的假塑性流动。与市售凝胶的20.83%相比，DCR非离子表面活性剂囊泡凝胶在3%羟丙基甲基纤维素（HPMC）中的药效学活性显著，最大抑制水肿大小为37.66%（p < 0.05）。这些结果表明，将DCR非离子表面活性剂囊泡掺入3% HPMC中用于局部应用，作为治疗骨关节炎的有效抗炎药物。
